Inert Ingredients in Pesticide Products
Inert Ingredients in Pesticide Products;
|CAS No.||Chemical Name|
|110-80-5||Ethanol, 2-ethoxy (cellulosive)|
|111-15-9||Ethanol ethoxy acetate|
|109-86-4||Ethylene glycol monomethyl ether; methyl cellulosive|
|77-83-8||Ethyl methyl glycidate|
|591-78-6||Methyl n-butyl ketone|
|78-87-5||Propylene dichloride (1,2-dichloropropane)|
|8003-34-5||Pyrethrins and pyrethroids|
|56-35-9||Tributyl tin oxide|
EPA has further identified about 60 inert ingredients which the Agency believes are potentially toxic and should be assessed for effects of concern (List 2). Many of these inert ingredients are structurally similar to chemicals known be toxic; some have data suggesting a basis for concem about the toxicity of chemical. Most of the chemicals on List 2 have been designated for testing through the National Toxicology, Program (NTP), the EPA Office of Toxic Substances (OTS) or other regulatory or government bodies. The FIFRA Scientific Advisory Panel has also reviewed this list. Because testing is ongoing for most of chemicals on List 2, it is expected to change periodically. It is the Agency's policy to have all additions, deletions or changes to List 1 or 2 reviewed by the FIFRA Scientific Advisory Panel. List 2 potentially toxic inerts/high priority for testing, is as follows:
LIST 2. POTENTIALLY TOXIC INERTS/HIGH PRIORITY FOR TESTING
|CAS No.||Chemical Name|
|85-68-7||Butyl benzy phthalate|
|112-34-5||Diethylene glycol monobutyl ether (butyl carbitol)|
|111-90-0||Diethylene glycol mono ethyl ether (carbitol)|
|111-77-3||Diethylene glycol mono methyl ether (methyl carbitol)|
|34590-94-8||Dipropylene glycol monomethyl ether|
|111-76-2||2-Butoxy-l-ethanol (ethylene glycol mono butyl ether)|
|5131-86-8||1-Butoxy-2-propanol (1,2-propylene glycollmono butyl ether|
|29387-86-8||Propylene glycol monobutyl ether|
|25498-49-1||Tripropylene glycol monomethyl ether|
|577-11-7||Dioctyl sodium sulfosuccinate|
|106-10-1||Methyl isobutyl ketone|
|25168-06-3||lsopropyl phenols. Petroleum hydrocarbons|
|80-62-6||Methyl methacrylate. Xylene-range aromatic solvents|
Inert ingredients were put on List 4 (minimal hazard or risk) if they were generally regarded as innocuous. These included inert ingredients such as cookie crumbs, corn cobs, and substances "generally recognized as safe (GRAS)" by the FDA (21 CFR Part 182). There are approximately 300 inert ingredients in this category.
An inert ingredient was placed on List 3 if there was no basis for listing it on any of the other three lists. There are approximately 800 inert ingredients in this category.
Lists 3 and 4 are not addressed further in this notice since the Agency will be taking no particular regulatory actions with respect to these inert ingredients at this time. Applications for exemptions from the requirement of tolerances for Lists 3 and 4 inert ingredients are discussed in unit VI.
These lists were developed to establish priorities for regulatory activities related to existing inert ingredients. The Agency intends to focus its initial regulatory efforts on the inerts of toxicological concern. For this reason, the current policy notice is most specific with regard to inert ingredients on List 1. As resources permit, EPA will extend its activities to the other inert ingredients.
IV. Inerts of Toxicological Concern (List 1)
In order to reduce the potential for adverse effects to humans or the environment it is the policy of the Agency to encourage the use in pesticide products of the least toxic inert ingredients available and to require development of the information necessary to determine the conditions under which various chemicals may be used safely as inert ingredients in pesticide products. In line with this policy, EPA has developed procedures for dealing with new and existing pesticide registrations containing inerts of toxicological concern. It should be noted that the Agency is currently engaged in a comprehensive review of various chlorinated solvents, several of which are on List 1or List 2. The data gathering described in Section A.3 below will support that effort. As conclusions are made in the Solvents Project, the inerts policy with respect to those substances will be reviewed to see whether adjustments in status would be appropriate. In the meantime, chemicals under review in the Solvents Project are subject to the requirements described below.
A. Existing Registrations
1. Substitution. Registrants are encouraged to substitute inert ingredients not included in List 1 or List 2 for inerts of toxicologic concern (List 1) now contained in their products. Reqistrants electing to substitute should submit a new Confidential Statement of Formula as a proposed amendment to the registration. The revised Confidential Statement of Formula should be sent to: Product Manager, Registration Division (TS-767C), Office of Pesticide Programs, Environmental Protection Agency, 401 M St. SW., Washington. DC 20460.
2. Labeling. As an immediate step to inform users and the general public of the presence of an inert of toxicological, concern, EPA is directing registrants of each product containing an inert ingredient on List 1 to submit applications (to the product manager at the above address) to amend their registrations to add the following statement to the label:
This product contains the toxic inert ingredient (name of inert).
T'he wording should be placed in close proximity to the ingredients statement in a type size comparable to other front panel text.
Registrants are required to submit the application not later than October 20, 1987. (At the top of each application, please write in bold letters "INERTS".) No pesticide product containing a List 1 inert ingredient may be released for shipment after October 20, 1988 unless the product bears an amended label which complies with the provisions listed above. EPA may initiate cancellation proceedings under section 6(b)(1) of FIFRA for any product registrations containing a List 1 inert ingredient for which an amended label is not submitted in a timely fashion.
3. Data Requirements. In addition, any registrant who retains an inert of toxicologic concern in his or her product(s) will be subject to data call-in under section 3(c)(2)(B) of FIFRA. The data requirements will take into consideration the chemical's existing data base and the product's use pattern. Because of the demonstrated biological activity of chemicals on List 1. EPA may require as much data as would be required by 40 CFR Part 158 for an active ingredient. For many of these inert ingredients, adequate toxicity data exist but additional exposure data would be required. In addition, data on environmental fate, ecological effects and residue chemistry may be required. The Agency intends to issue data call-in letters for this data beginning in April 1987.
4. Hearings. For certain inert ingredients on List 1, EPA intends to issue Notices of Intent to Hold a Hearing under FIFRA section 6(b)(2). The purpose of these hearings will be to gather and present information on the risks and benefits of these inert ingredients. Based on the information presented during that hearing EPA will determine whether pesticide products containing a particular inert ingredient on List 1 should be cancelled, be subject to additional restrictions, or be allowed to continue their current registrations without change. Hearings conducted under FIFRA section 6(b)(2) are formal adjudicatory proceedings conducted according to the procedures in 40 CFR Part 164. Evidence is presented under oath by witnesses, who are subject to cross-examination. EPA has the burden of proceeding, but the ultimate burden of proof rests on registrants. Decisions are based only on evidence in the hearing record. The presiding Administration Law Judge makes an Initial Decision which may be appealed to the Administrator who makes the Final Decision.
EPA expects to issue the first Notice of Intent to Hold a Hearing concerning an inert ingredient on List 1 in 1987. Subsequent notices may cover several List 1 inert ingredients with similar functions in pesticide formulations, e.g. solvents.
5. Reclassifying Inert Ingredients As Active Ingredients. The Agency has also identified several inerts of toxicological concern which are present in pesticide formulations to act against some pest, although not necessarily the pest targeted by the formulation. For example, an ingredient may be added to a rodent bait to repel flies. Although these ingredients have traditionally been designated as inert ingredients, EPA believes that they are actually active ingredients. These inert ingredients are formaldehyde, paraformaldehyde, hexachlorophene, 2,2-dichloro vinyl dimethyl phosphate, and the pyrethins/pyrethoids. EPA recently indicated its intent to reclassify formaldehyde and paraformaldehyde as active ingredients when used in pesticide products to prevent microbial damage to such products (52 FR 321, January 5, 1987). EPA intends to similarly reclassify the other inert ingredients that prevent damage to pesticide formulations by pests as active ingredients in those formulations. This will simplify the process of obtaining data under FIFRA section 3(c)(2)(B).
6. Revocation of Exemptions from Tolerance. Any pesticide chemical used on food must have a tolerance or an exemption from the need for tolerance. If the Agency determines that an inert of toxicological concern is no longer used in any food-use pesticide product, the exemption(s) from the need for a tolerance will be revoked for that inert ingredient. In addition, there may be circumstances in which EPA will replace existing exemptions with finite tolerances. Such action will be taken when the data gathered through the data call-in activities on inerts of toxicological concern enable the Agency to establish a finite tolerance.
B. New Registrations
In general, no new product that contains an inert of toxicological concern will be registered unless the product is closely similar to an existing product, as defined above. In limited circumstances, other products may be registered if review indicates that the risk of unreasonable adverse effects to humans or on the environment, will be decreased by such a registration. As specified above, the label of any product containing such an inert ingredient will be required to indicate the presence of the inert ingredient. In addition, the product will be registered conditionally, subject to any data requirements that the Agency imposes on registrants of similar products.
V. Potentially Toxic Inerts/High Priority for Testing
The Agency's goal is to collect enough information on each inert ingredient on List 2 to determine whether further actions such as those for inerts on List 1 are necessary. In order to make this determination, the Agency is monitoring ongoing testing and gathering existing information on the potential adverse effects of these substances and will require additional testing from industry if it is needed.
A. Existing Registrations
EPA does not plan to issue any specific requirements in the near future for inert ingredients on List 2. If an inert ingredient is moved from List 2 to List 1, as new data or information becomes available, it will become subject to the requirements outlined in Section IV of this notice.
B. New Registrations
Closely similar products containing List 2 inert ingredients will continue to be registered. Applications for registration of other products (e.g., new uses) containing inert ingredients that are on List 2 will be reviewed on a case-by-case basis. The Agency will consider the current weight-of-evidence with respect to the hazards posed as well as the potential for increased exposure when deciding whether the product meets the standard for registration.
VI. Inert Ingredients and New Food-Uses of Existing Inerts
Any inert ingredient proposed for use in a pesticide product is considered to be a "new" inert ingredient if it is not currently identified as present in some approved pesticide formulation or has never been in a previously registered product. The minimal data generally required to evaluate the risks posed by the presence of a new inert ingredient in a pesticide product is a subset of the kinds of data typically required for active ingredients under 40 CFR Part 158. A description of the data required and guideline number as listed in 40 CFR Part 158 follows:
DATA REQUIRED TO EVALUATE RISKS POSED BY INERT INGREDIENTS IN PESTICIDE PRODUCTS
|Guideline Ref. Number 40 CFR Part 158|
|1. KIND OF DATA REQUIRED:|
|Description of the pesticide type of pesticide formulation(s) in which the inert will be used and the maximum percent by weight it can occupy in any formulation.|
|Description regarding the range of use patterns and range of concentrations of the inert material 1||171-3|
|2. KIND OF DATA REQUIRED:|
|Description of the chemical or chemical mixture including structual formula(e)||61-1|
|Chemical Abstracts Services (CAS) Registry Number and file||61-1|
|Any technical bulletins available on the inert:|
|Purpose of the inert in pesticide formulation (i.e., solvent, emulsifier, etc.)||61-1|
|Discussion of possible toxic contaminants such as nitrosamines, polynuclear aromatics or dioxins||61-3|
|Batch analyses 2||62-1|
|Octanol/Water Partition Coefficient||63-11|
|90-day feeding study: rodent and dog 3||82-1|
|Subchronic Dermal toxicity 4||82-2, 82-3|
|Teratology study: rodent||83-3|
|Gene mutation test||84-2|
|Structural chromosomal aberration test||84-2|
|Other genotoxic effects||84-4|
|3. KIND OF DATA REQUIRED|
|Acute 96-hr fish LC50 (preferably in rainbow trout or bluegill)||72-1|
|48-hr LC50 or EC50 in daphnia||72-2|
|Avain oral LD50 (preferable in mallard or bobwhite)||71-1|
|8-day avian dietary (preferable in mallard or bobwhite)||71-2|
|Environmental Fate: 5|
|Aerobic soil metabolism||161-1|
|Photodegredation in water||161-2|
|Photodegredation in soil||161-3|
|Koc or Kd||163-1|
|1 For use on food crops, include whether preharvest and/or post-harvest applications, or use on livestock, and use any restrictions.|
|2 Batch analysis would be required only if there are possible contaminants of concern or if a mixture of variable composition is involved.|
|3 If the inert is used in a food-use product, two subchronic feeding studies will be required.|
|4 This study may be substituted for the 90-day feeding studies if only non-food use is proposed. The duration of the subchronic dermal study will depend on the potential duration and frequency of human exposure.|
|5 Ecotoxicology and environmental fate testing are required only for formulations used outdoors.|
In certain circumstances, EPA may waive some or all of these data requirements, for example, if the applicant can show that the proposed new use pattern of the inert ingredient will result in little or virtually no exposure. Data or use information should address dietary, groundwater or applicator exposure, as appropriate. In gathering the data to be submitted to the Agency, the applicant should contact manufacturers trade associations, etc., who may be able to assist in identifying appropriate data. As a minimum, applicants whose formulations contain new food-use inert ingredients should contact the FDA to obtain data and information on inert ingredients that may have approved food additive uses.
In addition to new inert ingredients, the data requirements and review process described above will be used to evaluate requests for additional exemptions from tolerances and changes in exemptions from tolerances of inerts already cleared for food-use and for exemptions from tolerances for existing inert ingredients not presently used on foods. The requirements outlined constitute our "base set" of data needs. If these studies indicate potential human health concerns or ecotoxicity or potential groundwater contamination, further testing may be required to fully assess the risks and define acceptable uses.
VII. Proprietary Inert Ingredients or Mixtures
In the case of some products, the registrant is not aware of the identity of all of the inert ingredients. These products contain a substance (usually a combination of several inert ingredients) which is designed to perform a particular function in pesticide products (e.g., to act as a solvent or emulsifier) but which is sold to pesticide registrants under a trade name without disclosure of the substance's constituents. The seller of such a substance typically will claim that the identity of the constituents in a trade secret. Many of these "proprietary inerts" are marketed in this manner today. EPA has allowed pesticide products containing such substances to be registered if the applicant for registration first arranged to have the supplier of the proprietary inert substance disclose its formula to EPA. This practice poses problems in administering the data call-in and labeling requirements contemplated by this Notice. For instance, EPA may know that a proprietary inert substance contains a List 1 inert ingredient, but may be unable to disclose that fact to the registrants of the products that contain the proprietary substance. EPA obviously cannot require these registrants to list the inert ingredient on their labels, or subject them to a data requirement, until the confidentiality problem is overcome. The approaches set forth below address this problem.
A. Existing Registration
If a product with an existing registration contains an inert of toxicological concern comprising part of a proprietary inert ingredient or mixture. The Agency will request the formulator of the ingredient or mixture to divulge the presence and identity of the inert of toxicological concern to the registrant so that the registrant can label the product properly. If the producer of the proprietary ingredient or mixture refuses to divulge this information, the Agency will require the formulator to justify the claim of confidential business information under 40 CFR Part 2. If EPA reviews the claim and determines that it is without merit, EPA will so inform the formulator of the ingredient or mixture. Thereafter, following the appropriate procedures in EPA regulations, EPA may inform registrants that the proprietary inert ingredient or mixture contains a specific ingredient. If EPA does not decide to disallow a CBI claim, EPA may none-the-less require, FIFRA under section 3(c)(2)(B), that the registrant provide EPA with information showing that the registrant knows the composition of the proprietary inert ingredient or mixture. In either case, once EPA has determined that a registrant is aware that his product contains an inert of toxicological concern which is present in a proprietary inert ingredient or mixture used to formulate the product, EPA will inform the registrant of the regulatory actions being initiated because of the presence of that inert ingredient.
B. Applications for New Registrations
If a registrant submits an application for a new use or identical or a substantially similar use containing an inert of toxicological concern as part of a proprietary inert ingredient or mixture, the Agency will notify the registrant that the product cannot be registered based on the inert ingredients which are contained in the formulation. It will be the responsibility of the registrant to contact the formulator/supplier of any proprietary ingredient or mixtures used in the pesticide formulation and determine the identity of the inert(s) of toxicological concern present in the pesticide formulation.
C . Registrant's Ongoing Responsibility for the Composition of the Pesticide Products
Units VII.A. and VII.B. discuss the procedures the Agency will employ to ensure that a registrant is aware that his product contains an inert of toxicological concern as part of a proprietary inert ingredient or mixture. With the exception of knowing about the presence of inerts of toxicological concern, the Agency does not at this time plan to require that an applicant know or find out the composition of a proprietary inert ingredient or mixture order to obtain registration. An applicant is, however, required to ensure that the Agency is informed of its composition by its producer.
In addition, the Agency does hold a registrant responsible for the certified limits of each inert ingredient in his product, including those that are present as part of a proprietary inert ingredient or mixture. An applicant who does not know the composition of an inert ingredient or mixture, and cannot persuade his supplier or producer to disclose it, may certify to an upper and lower limit of the ingredient or mixture as introduced into his product. In this case, the fact that the applicant uses a proprietary inert ingredient or mixture whose composition is not known to him does not remove his responsibility for maintaining the composition of each of those inert ingredients within it's certified limits and assuring that the composition of the proprietary inert ingredient(s) or mixtures(s) he uses will not change over time. EPA believes that contractual agreement between formulator and supplier is the best way to ensure that the formulator can rely on the composition of the material received short of having direct knowledge of its composition.
Dated: April 13, 1987
Assistant Administrator for Pesticides and Toxic Substances
(FR Doc. 87-8787 Filed 4-21-87; 8:45 am)
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